Case Comprehensive Cancer Center Standard Operating Procedures€¦ · Case Comprehensive Cancer Center Standard Operation Procedures for Clinical Research 2 5.2 Any other CWRU, UH

Case Comprehensive Cancer Center

Standard Operating Procedures

June 2011 (1st Edition) (Revisions: October 2012; November 2012; December 2012; January 2013;

February 2013; October 2013; September 2014; November 2014;

April 2015; May 2015; December 2015; July 2016; October 2016;

December 2016; April 2017; October 2017)


11100 Euclid Avenue, Wearn 152

Cleveland, Ohio 44106-5065


Standard Operation Procedures for Clinical Research

1

TABLE OF CONTENTS

Introduction

Contacts

Abbreviations

Standard Operating Procedures

1. General Administration (GA)

GA-1.1.0 Procedure for the Development, Review, Approval, Updating and

Maintaining of Standard Operating Procedures (Revised: January 2013; April 2015;

May 2017)

2. [Reserved]

3. OnCore® Clinical Trials Management System (OC)

a. OC-3.1.0 Registration of Case CCC Personnel in the OnCore® Database (Added:

November 2011; Revised: November 2012; December 2012; February 2013; June

2017)

b. OC-3.2.0 Registration of Non-Case CCC Personnel in the OnCore® Database (Added:

August 2017)

4. Trial Registration (TR)

a. TR-4.1.0 NCI Clinical Trials Reporting (CTRP) (Revised: September 2012; May 2015;

June 2017)

b. TR-4.2.0 Registration of Clinical Trials on ClinicalTrials.gov

(Revised: September 2012; April 2015; June 2017)

c. TR-4.3.0 Clinical Trials Results Reporting with ClinicalTrials.gov

(Added: October 2012; Revised: February 2014; April 2015; June 2017)

5. Project Management (PM)

a. PM-5.1.0 Transfer of the Lead Institution Responsibilities to the Secondary Institution

for Joint Cancer-Related Research Studies (Revised: May 2015)

b. PM-5.2.0 Responsibilities of the Lead Institution for Joint Cancer-Related Research

Studies

6. Subject Management (SM)

a. SM-6.1.0 Secondary Review of Eligibility for Therapeutic Clinical Trials (Revised:

January 2013; December 2015; July 2016)

b. SM-6.2.0 Verification and Confirmation of Independent Review of Patients’ Responses

on Investigator-Initiated Clinical Trials (Added: October 2013; Revised: December

2016)

7. Data Safety and Toxicity Committee (DSTC) / Data and Safety and Monitoring (DSM)

a. DSTC/DSM-7.1.0 Submission of Documents to the Data Safety and Toxicity

Committee (Added: September 2014)

b. DSTC/DSM-7.2.0 Submission of Continuing Reviews to the Data Safety and Toxicity

Committee (Added: September 2014)

c. DSTC/DSM-7.3.0 Data Safety and Toxicity Committee Reporting and Communicating

Action Items (Added: September 2014)

http://clinicaltrials.gov/



2

8. Auditing and Monitoring [Quality Assurance] (QA)

a. QA-8.1.0 Monitoring Investigator-Initiated Clinical Trials

(Revised: September 2012; May 2015)

9. Regulatory Affairs (RA)

a. RA-9.1.0 Statement of Investigator (Form FDA 1572) (Revised: October 2016)

b. RA-9.2.0 Regulatory Documentation Management (Revised: September 2012)

10. Protocol Review and Monitoring Committee (PRMC)

a. PRMC-10.1.0 Protocol Review and Monitoring Committee Submission (Revised: April

2015; April 2017)

b. PRMC-10.2.0 Protocol Review and Monitoring Committee Amendment Submission

(Revised: April 2015; June 2017)

c. PRMC-10.3.0 Protocol Review and Monitoring Committee Accrual Monitoring

(Added: November 2011; Revised November 2012; April 2015; June 2017)

d. PRMC-10.4.0 A Centralized Scientific Review (CSR) for the Ohio Clinical Trials

Cooperative (OCTC) (Added: November 2014; Removed: June 2017)



3

INTRODUCTION

Standard Operating Procedures (SOPs) apply to those members of the clinical research team who are

involved in conducting cancer research and clinical trials at the Case Comprehensive Cancer Center.

The Cancer Center implements and enforces all SOPs across consortium institutions – Case Western

Reserve University, Cleveland Clinic Foundation and University Hospitals.

The clinical research team includes the following personnel: Principal Investigator; Co-Investigator;

Site Investigator; Research Nurse; Clinical Research Associate / Coordinator; Regulatory Coordinator;

Data Analyst / Coordinator; Quality Assurance Manager; Biostatistician; Support Staff; Other

Personnel, as applicable.

CONTACTS

Associate Director for Clinical Research

Mitchell Machtay, MD, Professor

Tel. 216/286-6740; E-mail: [email protected]

Deputy Associate Director for Clinical Research; Director for Clinical Trials

Mikkael Sekeres, MD, Professor

Tel. 216-445-9353; E-mail: [email protected]

Medical Director, Clinical Research Office

Smitha Krishnamurthi, MD, Assistant Professor


Administrative Director, Case CCC Clinical Research Office

Katarzyna Karelus, MS, MBA


http://www.cwrumedicine.org/component/zoo/?view=item&item_id=147



4

ABBREVIATIONS

ADE Adverse Drug Event/Experience

ADR Adverse Drug Reaction

AE Adverse Event

Case CCC Case Comprehensive Cancer Center

CCF Cleveland Clinic Foundation

CFR Code of Federal Regulations

COI Conflict of Interest

CRA Clinical Research Associate

CRC Clinical Research Coordinator

CRF Case Report Form

CRO Case CCC Clinical Research Office

CRO Contract Research Organization

C-ROC Clinical Research Operations Committee

CTRP Clinical Trials Reporting Program

CTU Clinical Trials Unit

CTWG Clinical Trials Working Group

CWRU Case Western Reserve University

DSM Data and Safety Monitoring

DSMB Data and Safety Monitoring Board

DSMP Data and Safety Monitoring Plan

DSTC Data Safety and Toxicity Committee

FDA Food and Drug Administration

GCP Good Clinical Practice

IBC Institutional Biosafety Committee

ICF Informed Consent Form

ICH International Conference on Harmonization

IDE Investigational Device Exemption

IND Investigational New Drug

IRB Institutional Review Board

NCI National Cancer Institute

NCT National Clinical Trial

OBA Office of Biotechnology Activities

OHRP Office for Human Research Protections

OnCore® Clinical Trials Management System

PI Principal Investigator

PRMC Protocol Review and Monitoring Committee

QA Quality Assurance

QC Quality Control

QOL Quality of Life

SAE Serious Adverse Event

SOP Standard Operating Procedure

UH University Hospitals

Case Comprehensive Cancer Center Standard Operation Procedures for Clinical Research

SECTION 1: GENERAL ADMINISTRATION (GA)



1

Title: Procedure for the Development, Review, Approval, Updating and Maintaining of

Standard Operating Procedures (SOPs)

SOP #: GA-1.1.0

Version #: 4.0

Original Approval Date: May 3, 2011

Effective Date:

July 3, 2011

Revision Dates:

January 7, 2013

April 7, 2015

May 16, 2017

1.0 Standard Operating Procedure Statement/ Purpose/Background

To define parameters and a process for establishing and maintaining all of Case

Comprehensive Cancer Center (Case CCC) clinical research guidelines and procedures.

To define expectations regarding harmonization between Case CCC institutional research

policies.

2.0 Scope All cancer research activities and processes that involve any Case CCC institution,

department and institute.

3.0 Responsibility Case CCC Clinical Research Operations Committee (C-ROC).

4.0 Definitions 4.1 Definitions: Terminology to clarify intent of message.

4.2 SOP Number: Alphanumeric number of SOPs reflecting the SOP category and

number within that category.

4.3 Original Approval Date: Date of the C-ROC meeting when a given SOP was

approved.

4.4 Effective Date: The date when the policy became active.

4.5 Revisions Dates: Date of the C-ROC meeting when revisions were approved.

4.6 SOP Statement/Purpose/Background: An SOP general statement and a brief

description of the SOP purpose and/or background.

4.7 Procedure: A predetermined course of action established as a guide/instructions

towards acceptable actions and objectives.

4.8 References: Any/all references to support the SOP.

4.9 Appendices: Supplemental documents in support of the SOP.

5.0 Procedure 5.1 Policy Development, Review and Approval

5.1.1 All elements provided in the Definitions section 4.0 above are required

as applicable.


SECTION 2: EDUCATION AND TRAINING (ET)


SECTION 3: ONCORE CLINICAL TRIALS DATABASE (OC)


1

Title: Registration of Case CCC Personnel in the OnCore® Database

SOP #: OC-3.1.0

Version #: 3.0

Original Approval Date: October 4, 2011

Effective Date:

November 4, 2011

Revision Dates:

November 6, 2012

November 21, 2012

December 4, 2012

February 5, 2013

(Appendix I)

June 21, 2017

1.0 Standard Operating Procedure Statement / Purpose / Background

To provide access and register Case Comprehensive Cancer Center (Case CCC), Case

Western Reserve University (CWRU), University Hospitals (UH) and Cleveland Clinic

personnel in the OnCore database.

2.0 Scope

The OnCore database contains data for all the cancer clinical trials conducted by the Case

CCC. Case CCC, CWRU, UH and Cleveland Clinic personnel, as described in Section 5.1.4

below, that request access to the OnCore database to either input information or utilize

information for research purposes, will need to undergo vetting process as per this SOP in

order to be considered to be registered and granted access in the OnCore database.

3.0 Responsibility

It is the responsibility of the OnCore Registration Coordinator to register personnel. The

OnCore registration coordinator can be reached at [email protected].

4.0 Definitions

4.2 OnCore® Clinical Trials Management System (referred to as OnCore): database to track

information from clinical trials conducted by the Case CCC.

4.3 HIPS: The Health Information Privacy and Security.

4.4 OnCore Learning Portal: training videos and documents for the OnCore database.

4.5 SRE: Secure Research Environment

4.6 CWRU [U]Tech: CWRU information technology services

4.7 Tenant Coordinator: SRE account manager

5.0 Eligible Users

5.1 The following personnel can request and may receive access to OnCore database based

on their employment, qualifications and needs: Case CCC members; people actively

involved in conducting and managing research studies and clinical trials at CWRU, UH

and Cleveland Clinic and their satellites; respective IRB offices staff, and IRB Chairs

and Co-Chairs.

mailto:[email protected]


2

5.2 Any other CWRU, UH and Cleveland Clinic faculty and/or staff outside the above listed

categories will be required to write a letter addressed to the Case CCC Associate

Director for Clinical Research and copy the Registration Coordinator, requesting and

justifying his/her specific access to OnCore. Requests will be reviewed by the Case

CCC Associate Director for Clinical Research and Registration Coordinator. Access will

be considered on a case by case basis.

6.0 Procedure

6.1 Complete the SRE User Enrollment and OnCore Access Form on the Case CCC

website: http://cancer.case.edu/research/clinical-research-office/oncore/. (Appendix I)

6.1.1 E-mail accounts are required to be institutionally provided, i.e. case.edu,

ccf.org, uhhospitals.org (accounts such as yahoo, g-mail, etc. cannot be used).

6.1.2 The supervisor must sign off on the Form, provide his/her contact information

and check the appropriate role/roles for the new user.

6.1.3 Email completed form to: [email protected].

6.2 Activate CWRU Network ID and Complete CITI HIPS Training

6.2.1 The OnCore registrar will acquire a CWRU ID for the new user.

6.2.2 The new user will receive an email from [email protected] with their

CWRU ID and instructions to set up a password for their CWRU account.

6.2.3 The new user will set up their CWRU email account

(https://www.case.edu/utech/cwru-email/).

6.2.3.1 This email address can be forwarded to your primary email account

6.2.4 Set up DUO login with CWRU:

6.2.4.1 Instructions at: https://www.case.edu/its/information-security/duo/

6.2.5 Email [email protected] when Duo Security and CWRU account

are set up.

6.2.6 All Case CCC consortium members must submit their CITI HIPS training

certification to [email protected] and submit continuing renewals

every 3 years.

6.3 Activate SRE account:

6.3.1 Upon completion of the above steps (6.1 and 6.2) the OnCore registrar will

apply for an SRE account for the user with CWRU [U]Tech.

6.3.1.1 Registrar will complete page 2 of the SRE User Enrollment and

OnCore Access Form and send it to CWRU [U]Tech. An electronic

copy will be kept in OnCore

6.3.1.2 [U]tech service will create the new user’s account and provide an

SRE password sent to their work email.

6.4 Training

6.4.1 The new user will be contacted via e-mail or phone to set up training.

6.4.1.1 Cleveland Clinic employees should contact Cleveland Clinic OnCore

administrator.

6.4.1.2 UH and CWRU employees will be contacted by the OnCore

administrator

6.4.2 Once training is complete the trainer will sign the sections of the training log

appropriate to the user’s roles (Appendix II)

6.4.3 Upon completion of training the user will receive a login and password to

OnCore with their assigned roles.

6.5 Maintenance of OnCore Users

http://cancer.case.edu/research/clinical-research-office/oncore/


https://www.case.edu/its/information-security/duo/


https://its-services.case.edu/my-case-identity/affiliates/request/



https://sreportal.case.edu/

https://www.citiprogram.org/default.asp




4

APPENDIX I

SRE User Enrollment and OnCore Access 1. SRE Access Requested Role: Application: Request Type:

Researcher OnCore New User Clinician Labmatrix Renewal Admin (Research Support) APEX Access Modification

Nurse

2. SRE User Information

Last Name Middle Initial First Name Case Net ID

Work Email Work Phone Alt. Phone

Work Address City ZIP Code DOB

Department: Job Title

Employer: UH CC CWRU Other (specify) Title Credentials: MD DO PhD RN 3. SRE Applicant Acknowledgement (read and sign)

You must be located physically at an SRE approved facility.

You agree to complete a “Securing the Human” training.

You agree to use SRE in accordance with all applicable laws and Case’s “Acceptable Use of Computing and Information Technology Resources” policy: http://www.case.edu/its/security/docs/aup.html

By signing below, a SRE applicant acknowledges that the information they have provided is accurate and that they will follow applicable policies and standards.

The SRE is not connected to the Internet. In order to provide a secure controlled environment there is no outside connectivity to websites and other network resources. This includes email, web search, social media, reference sites such as wikis, or any other web property.

Data transmissions are monitored. By default the SRE is monitored for malicious activity. This includes gaining access to systems that you are not authorized to use. Please report any misuse to the ITS help desk.

I will not log on to the system in order to provide another person access to the system.

I agree to abide by Federal and Institutional HIPAA and HITEC guidelines and related activities concerning data and patient information.

_____________________________ ___________________

Printed SRE User Name SRE User Signature Date 4. Supervisor Information

Printed Supervisor Name Phone Number Supervisor Signature_________________________________________ To be completed by Supervisors (indicate access rights)

Registering Subject Regulatory Read Data Entry Financial


5

APPENDIX II

TRAINING LOG

Instructions: Log into the SRE website at https://sreicboncore.case.edu using the CWRU id and SRE password given to you. Click on the ICB OnCore link. Log in using your OnCore id and OnCore password. You will be asked to change your password. Once training is complete return this signed log to [email protected]. Upon receipt your new role will be assigned.

User Name: Document File Name Date Signed

ALL Users

General Tips & Navigation Reference

OnCore Personalization - Home Screen Configuration

OnCore Searches: Protocol, Subject, and Document

Audit (AUDIT)

Audit Console Tutorial

Clinical Research Associate (CRA)

New Subjects Registration

Pre-Screening Overview

Subject Administration

Subject Search Overview

Subject Visit Tracking and Forms

Data Manager (DMAN)


Online Forms Monitoring Overview (DM Console)

Data Safety and Monitoring (DSMC)

DSMC Audit Overview

DSMC Console Overview

OSR Management Overview

Finance (FIN)

Financial Console Overview

Charge Master Overview

Regulatory (REG); (PRMC)

Protocol Administration Overview

SIP Product Overview

Managing Protocol task lists

Protocol Investigator (PI)

PI Console

Statistician (ST)

Biostat Console Overview

Access Log Overview

Accrual Monitoring Overview

Biospecimen Management (BSM)

OnCore Admin Sign off:

https://sreicboncore.case.edu/



6

APPENDIX III

SRE Bulk Access Change Form

Case Western Reserve’s University’s Secure Research Environment (SRE) is intended to be used by authorized individuals for the purpose of securely handling research data. SRE user access shall not exceed 365 days without Study Official review and reauthorization of access. SRE access for the individuals listed below is expected to expire in the near future. Please review the information below to determine appropriate renewal status. Acknowledge access renewals by placing an X next the appropriate SRE ID. The SRE Bulk Access Change Form facilitates the bulk renewal of account access for 365 days. User access renewals requiring specific changes to access and resources should use the “SRE Enrollment and Access Change Form”. -----------------------------------------------------------------------------------------------------------------------------------------

Renew

NetID First Name Last Name Training Confirmation

Tenant Coordinator Acknowledgement By signing below, the study coordinator acknowledges that they have reviewed the provided information, verified required training completion, and renewed SRE access for selected individuals for a period of 365 days.

Printed Tenant Coordinator Name

Tenant Coordinator Signature Date


1

Title: Registration of Non-Case CCC Personnel in the OnCore® Database

SOP #: OC-3.2.0

Version #: 1.0

Original Approval Date: August 1, 2017

Effective Date:

September 1, 2017

Revision Dates:


To provide access and register users from institutions outside of the Case Comprehensive Cancer

Center (Case CCC) in the OnCore Database. All OnCore users from outside Case CCC must be

working on studies sponsored by Case CCC.

2.0 Scope

The OnCore database contains data for all the cancer clinical trials conducted by the Case CCC.

Users outside of the Case CCC consortium, that request access to the OnCore database to either

input information or utilize information for research purposes, will need to undergo vetting

process as per this SOP in order to be considered to be registered and granted access in the

OnCore database.

3.0 Responsibility

It is the responsibility of the OnCore Registration Coordinator to register personnel. The OnCore

registration coordinator can be reached at [email protected].

4.0 Definitions

4.2 OnCore Clinical Trials Management System (referred to as OnCore): database to track

information from clinical trials conducted by the Case CCC.

4.3 HIPS: The Health Information Privacy and Security.

4.4 OnCore Learning Portal: training videos and documents for the OnCore database.

4.5 SRE: Secure Research Environment

4.6 CWRU [U]Tech: CWRU information technology services

4.7 VDI: Virtual desktop infrastructure. Used to access OnCore from outside Case CCC

4.8 Tenant Coordinator: SRE account manager

5.0 Procedure

5.1 Complete the SRE User Enrollment and OnCore Access Form, available on the Case CCC

website: http://cancer.case.edu/research/clinical-research-office/oncore/. (Appendix I)

5.1.1 E-mail accounts are required to be institutionally provided (accounts such as

yahoo, g-mail, etc. cannot be used).

5.1.2 The supervisor must sign off on the Form, provide his/her contact information and

check the appropriate role/roles for the new user.

5.1.3 Email completed form to: [email protected].

5.2 Activate CWRU Network ID

5.2.1 The OnCore registrar will acquire a CWRU ID for the new user.





2

5.2.2 The new user will receive an email from [email protected] with their CWRU

ID and instructions to set up a password for their CWRU account.

5.2.3 The new user will set up their CWRU email account

(https://www.case.edu/utech/cwru-email/).

5.2.3.1 This email address can be forwarded to your primary email account

5.2.4 Set up DUO login with CWRU:

5.2.4.1 Instructions at: https://www.case.edu/its/information-security/duo/

5.2.5 Email [email protected] when Duo Security and CWRU account are

set up.

5.3 User must submit CITI HIPS training certification to [email protected]. If CITI

HIPS training is not available, training will be requested for the user by the OnCore

Registrar from the CWRU Compliance Office. Both CITI training or the provided security

training must be renewed every 3 years.

5.4 Activate SRE account:

5.4.1 Upon completion of the above steps (6.1-6.3) the OnCore registrar will apply for

an SRE account for the user with CWRU [U]Tech.

5.4.1.1 Registrar will complete page 2 of the SRE User Enrollment and OnCore

Access Form and send it to CWRU [U]Tech. An electronic copy will be

kept in OnCore

5.4.1.2 [U]tech service will create the new user’s account and provide an SRE

password sent to their work email.

5.4.1.3 If the user has arranged to work through the SRE web portal, the user’s

IP address must be provided to [U]Tech with submission of the SRE

Access form

5.4.1.4 If user will be using the virtual desktop infrastructure (VDI) to access

OnCore, no IP address is required.

5.4.1.5 Users within the VDI cannot save or print from OnCore

5.5 Training

5.5.1 The new user will be contacted via e-mail or phone to set up training.

5.5.1.1 Users working with a Cleveland Clinic led study should contact

Cleveland Clinic OnCore administrator.

5.5.1.2 Users working with a UH or CWRU led study will be contacted by the

OnCore registrar

5.5.2 Once training is complete the trainer will sign the sections of the training log

appropriate to the user’s roles (appendix II)

5.5.3 Upon completion of training the user will receive a login and password to OnCore

with their assigned roles.

5.6 Maintenance of OnCore Users

5.6.1 A report (Inactive Users 120 Days) is run every 6 months from the OnCore

database. This report lists users that have not logged into OnCore in the past 120

days. These users will be inactivated, disabling their login to OnCore. The

purpose of this is to update and delete users that are no longer active.

5.6.2 SRE and CWRU affiliate accounts expire annually and must be renewed by the

OnCore Registrar

5.6.2.1 Once a month, CWRU [U]Tech will send the OnCore Registrar a list of

all SRE users with account expiration dates

5.6.2.2 OnCore Registrar will use the SRE Bulk Access Change form to renew

all active OnCore User accounts expiring in the next 60 days (Appendix

III).

https://www.case.edu/its/information-security/duo/






https://www.citiprogram.org/default.asp




4

APPENDIX I

SRE User Enrollment and OnCore Access

1. SRE Access Requested Role: Application: Request Type:

Researcher OnCore New User Clinician Labmatrix Renewal Admin (Research Support) APEX Access Modification

Nurse

2. SRE User Information

Last Name Middle Initial First Name Case Net ID

Work Email Work Phone Alt. Phone

Work Address City ZIP Code DOB

Department: Job Title

Employer: UH CC CWRU Other (specify) Title Credentials: MD DO PhD RN

3. SRE Applicant Acknowledgement (read and sign)

You must be located physically at an SRE approved facility.

You agree to complete a “Securing the Human” training.

You agree to use SRE in accordance with all applicable laws and Case’s “Acceptable Use of Computing and Information Technology Resources” policy: http://www.case.edu/its/security/docs/aup.html

By signing below, a SRE applicant acknowledges that the information they have provided is accurate and that they will follow applicable policies and standards.

The SRE is not connected to the Internet. In order to provide a secure controlled environment there is no outside connectivity to websites and other network resources. This includes email, web search, social media, reference sites such as wikis, or any other web property.

Data transmissions are monitored. By default the SRE is monitored for malicious activity. This includes gaining access to systems that you are not authorized to use. Please report any misuse to the ITS help desk.

I will not log on to the system in order to provide another person access to the system.

I agree to abide by Federal and Institutional HIPAA and HITEC guidelines and related activities concerning data and patient information.

_____________________________ ___________________

Printed SRE User Name SRE User Signature Date 4. Supervisor Information

Printed Supervisor Name Phone Number Supervisor Signature_________________________________________ To be completed by Supervisors (indicate access rights)

Registering Subject Regulatory Read Data Entry Financial


5

APPENDIX II

TRAINING LOG

Instructions: Log into the SRE website at https://sreicboncore.case.edu using the CWRU id and SRE password given to you. Click on the ICB OnCore link. Log in using your OnCore id and OnCore password. You will be asked to change your password. Once training is complete return this signed log to [email protected]. Upon receipt your new role will be assigned.

User Name: Document File Name Date Signed

ALL Users

General Tips & Navigation Reference

OnCore Personalization - Home Screen Configuration

OnCore Searches: Protocol, Subject, and Document

Audit (AUDIT)

Audit Console Tutorial

Clinical Research Associate (CRA)

New Subjects Registration

Pre-Screening Overview

Subject Administration

Subject Search Overview


Data Manager (DMAN)


Online Forms Monitoring Overview (DM Console)

Data Safety and Monitoring (DSMC)

DSMC Audit Overview

DSMC Console Overview

OSR Management Overview

Finance (FIN)

Financial Console Overview

Charge Master Overview

Regulatory (REG); (PRMC)

Protocol Administration Overview

SIP Product Overview

Managing Protocol task lists

Protocol Investigator (PI)

PI Console

Statistician (ST)

Biostat Console Overview

Access Log Overview

Accrual Monitoring Overview

Biospecimen Management (BSM)

OnCore Admin Sign off:


6

APPENDIX III

SRE Bulk Access Change Form Case Western Reserve’s University’s Secure Research Environment (SRE) is intended to be used by authorized individuals for the purpose of securely handling research data. SRE user access shall not exceed 365 days without Study Official review and reauthorization of access. SRE access for the individuals listed below is expected to expire in the near future. Please review the information below to determine appropriate renewal status. Acknowledge access renewals by placing an X next the appropriate SRE ID. The SRE Bulk Access Change Form facilitates the bulk renewal of account access for 365 days. User access renewals requiring specific changes to access and resources should use the “SRE Enrollment and Access Change Form”. -----------------------------------------------------------------------------------------------------------------------------------------

Renew

NetID First Name Last Name Training Confirmation

Tenant Coordinator Acknowledgement By signing below, the study coordinator acknowledges that they have reviewed the provided information, verified required training completion, and renewed SRE access for selected individuals for a period of 365 days.

Printed Tenant Coordinator Name

Tenant Coordinator Signature Date


SECTION 4: TRIAL REGISTRATION (TR)


Page 1 of 5

Title: National Cancer Institute Clinical Trials Reporting Program (CTRP)

SOP #: TR-4.1.0

Version #: 4.0

Original Approval Date: July 5, 2011

Effective Date:

August 5, 2011

Revision Dates:

September 4, 2012

May 5, 2015

June 21, 2017

1.0 Standard Operating Procedure Statement / Purpose / Background To document the process for registering and maintaining protocols with the

National Cancer Institute (NCI) Clinical Trials Reporting Program (CTRP).

2.0 Scope As a NCI-designated comprehensive cancer center, the Case Comprehensive Cancer

Center (Case CCC) is required to register all interventional clinical cancer trials

(investigator-initiated (IIT) and proprietary) that were open to accrual as of January

1, 2009. NCI-designated cancer centers are also required to report accrual data for

IIT and proprietary trials for studies open to accrual as of January 1, 2012.

3.0 Definitions 3.1 OnCore® Clinical Trials Management System (referred to as OnCore):

Database to track information from clinical trials conducted by the

Case CCC.

3.2 CTRP Registration Coordinator: Person responsible for registering and

maintaining trials. Member of the Clinical Research Office.

3.3 Proprietary Trials: Industry-sponsored trials.

3.4 Study Personnel: Personnel responsible for entering data into OnCore.

Required fields in OnCore for CTRP registration are listed in Appendix

I.

4.0 Procedure The Case CCC Clinical Research Office CTRP registration coordinator is

responsible for registering trials with CTRP.

4.1 Communication: New trials are put into the OnCore database by the

Protocol Review and Monitoring Committee (PRMC) manager.

Notification of PRMC approval is automatically sent to the CTRP

registration coordinator through the OnCore database. As trials are

reviewed and approved by the University Hospitals IRB and the

Cleveland Clinic IRB, the approval information is entered into OnCore.

IRB notification is generated by the regulatory coordinator in OnCore

and is sent to the CTRP registration coordinator. IIT Trials are

registered in the CTRP database after IRB approval. Trials not

sponsored by Case CCC are registered after PRMC approval. Trials are

required to be registered prior to enrolment of the first subject.


Page 2 of 5

4.2 Sponsors other than Case CCC:

4.2.1 Cooperative Group trials: These groups are responsible for

registering their respective trials in CTRP. Therefore, these trials

are not registered by Case CCC registration coordinator.

4.2.2 Outside Investigator Initiated Trials (IIT): When Case CCC is

participating on an IIT sponsored by another institution, the lead

institution is responsible for adding Case CCC as a site in CTRP

and any accrual to the CTRP accrual website.

4.2.2.1 When another institution is participating on a Case CCC

investigator initiated trial, Case CCC is responsible for

adding all participating sites to CTRP and any accrual

from these sites to the CTRP accrual website.

4.2.3 Proprietary trials: If the trial is not already in CTRP, these trials

can be uploaded by the registration coordinator at any of the

participating sites from ClinicalTrials.gov

4.2.3.1 Participating Site for proprietary trials: The CTRP

registration coordinator is responsible for adding Case

CCC to trials already registered in CTRP.

4.3 Registration of Case CCC sponsored trials: All information and the

required documents (IRB approval letter, protocol and consent form)

are obtained from OnCore after initial IRB approval. Study personnel

are responsible for entering this information in OnCore ( Appendix I).

Upon acceptance of a trial registration in CTRP, a NCI # is assigned to

the protocol. The NCI # is entered in the management screen of

OnCore by the CTRP registration coordinator.

4.4 Review Information: Registration confirmation emails are sent within

24 hours from CTRP to the registration coordinator. Within 8-10

business days CTRP sends a Trial Summary Report (TSR) and xml file

to the registration coordinator. The registration coordinator reviews the

TSR and sends corrections, as applicable, to CTRP at

[email protected]. The xml file may be used for Clinicaltrials.gov

registration.

4.5 Maintenance: Protocol amendments and status changes are entered in

OnCore by study personnel and notification is then sent to the CTRP

registration coordinator. Amendment and status updates are registered

with CTRP upon notification. Amendments are required to be

registered with CTRP within 20 days of IRB approval. Revised

protocol, consent, IRB approval letter and summary of changes

documents are sent with the amendment update. Protocol status

definitions are listed in Appendix II.

4.5.1 Amendment changes may include PI, title, sites,

objectives/outcomes, study design and eligibility criteria.

4.5.2 All dates of the CTRP registration and maintenance processes

are recorded on an OnCore checklist.

4.6 Accrual Reporting: required quarterly to the CTRP accrual website

(https:// trials.nci.nih.gov/accrual/home.action)

4.6.1 Proprietary Trials: only requires summary accrual

4.6.2 Investigator-initiated Trials: report from OnCore is exported for

all trials open during any part of a quarter. This report includes

demographic information for individual subjects including the


https://trials.nci.nih.gov/accrual/home.action

https://oncore.cwru.edu/

https://trials.nci.nih.gov/

https://trials.nci.nih.gov/accrual/home.action

http://www.cancer.gov/clinicaltrials



Page 4 of 5

Appendix I

Required OnCore Data Fields for NCI-Clinical Trials Reporting Program (CTRP)

1. Lead organization trial identifier 2. Title 3. Phase 4. Trial type (intervention or non-interventional) 5. Primary Purpose (treatment, prevention, supportive care, screening,

diagnostic, health services research, basic science, other) 6. Accrual disease terminology (e.g. ICD9) 7. Lead Organization 8. Principal Investigator 9. Sponsor 10. Responsible Party (sponsor, investigator, sponsor-investigator) 11. Data Table 4 funding sponsor type (institutional, national group,

externally peer-reviewed, industrial) 12. Data Table 4 funding sponsor 13. NIH grant information

a. Funding mechanism (e.g. P30) b. Institution code (AA, AE, CA, etc.) c. Serial Number d. NCI Division/Program Code (OD, CCR, CIP, etc.)

14. Trial Status a. Status Date b. Status

15. Start Date 16. Primary Completion Date 17. IND information (if applicable)

a. IND/IDE type b. IND/IDE number c. IND/IDE Grantor (CBER, CDRH, CDER) d. IND/IDE Holder Type (industry, investigator, NCI, etc.) e. NIH Institution f. Expanded Access (yes/no)

i. If yes, expanded access type g. Exempt (yes/no)

18. Oversight Authority country 19. Trial Oversight authority organization (institutional review board,

FDA) 20. FDA regulated intervention indicator (yes/no) 21. Section 801 indicator (yes/no) 22. Delayed posting indicator (yes/no) 23. Data monitoring committee (yes/no) 24. Protocol: must include principal investigator’s contact information:

name, address, phone number, email and sponsor organization: name, address, email and lead organization: name, address, email)

25. IRB approval letter 26. Summary of changes for amendments 27. Informed Consent


Page 5 of 5

Appendix II Protocol Status Definitions

CTRP Clinicaltrials.gov In Review: Trial is currently under IRB review Not yet recruiting: participants are not yet being

recruited. This also applies to approved studies in CTRP

Approved: Trial has been IRB approved

Withdrawn: Trial has been withdrawn from development and review prior to enrollment of first participant. **

Withdrawn: trial halted prematurely, prior to enrollment of first participant **

Active: Trial is open for accrual

Recruiting: participants are currently being recruited

Temporarily Closed to Accrual: Trial is temporarily not accruing. **

Suspended: recruiting or enrolling participants has halted prematurely but potentially will resume **

Temporarily Closed to Accrual and Intervention: Trial is temporarily not accruing. Participants are not receiving intervention. **

Closed to Accrual: Trial has been closed to participant accrual. Participants are still receiving treatment/intervention.

Active, not recruiting: study is ongoing (i.e., patients are being treated or examined), but participants are not currently being recruited or enrolled

Closed to Accrual and Intervention: Trial has been closed to participant accrual. No participants are receiving treatment/intervention, but participants are still being followed according to the primary objectives of the study.

Administratively Complete: Trial has been completed prematurely (for example, due to poor accrual, insufficient drug supply, IND closure, etc.) **

Terminated: recruiting or enrolling participants has halted prematurely and will not resume; participants are no longer being examined or treated **

Complete: Trial has been closed to accrual and follow-up. Participant treatment/intervention has been completed and participants are no longer monitored for trial endpoints (i.e., last patient's visit has occurred). The trial has met its objectives.

Completed: The study has ended normally, and participants are no longer being examined or treated (that is, the "last subject, last visit" has occurred).

Primary Completion Date: date that the final subject was examined or received an intervention for the purposes of final collection of data for the primary outcome, whether the clinical trial concluded according to the pre-specified protocol or was terminated.

Primary Completion Date: date that the final subject was examined or received an intervention for the purposes of final collection of data for the primary outcome, whether the clinical trial concluded according to the prespecified protocol or was terminated.

Completion Date: The date that the trial has been closed to accrual and follow-up. Participant treatment/intervention have been completed and participants are no longer monitored for trial endpoints. The trial has met its objectives

Study Completion Date: Final date on which data was (or is expected to be) collected.

** Reason must be stated as to why trial stopped. ** Reason must be stated as to why study stopped.


1

Title: Registration of Clinical Trials on ClinicalTrials.Gov

SOP #: TR-4.2.0

Version #: 4.0


Effective Date:

July 3, 2011

Revision Dates:

September 4, 2012

April 7, 2015

June 21, 2017


To document the process for registering and maintaining trials with

Clinicaltrials.gov.

2.0 Scope: The U.S. Food and Drug Administration (FDA) is the government agency that

requires registration of clinical trials. The ClinicalTrials.gov website is maintained by

the National Library of Medicine (NLM) at the National Institutes of Health (NIH)

2.1 The Food and Drug Administration Amendments Act of 2007 (FDAAA

or US Public Law 110-85) passed on September 27, 2007 requires

mandatory registration and results reporting for certain clinical trials of

drugs, biologics, and devices. Case Comprehensive Cancer Center

(Case CCC) is required to register applicable clinical trials within 21

days of enrollment of first participant. Results from the clinical trials

must be registered within 1 year of completing data collection for the

pre-specified primary outcome. The purpose of this law is intended to

facilitate enrollment in clinical trials, allow for tracking of the progress

of such trials and address problems with the lack of timely

dissemination of research findings.

2.2 The International Committee of Medical Journal Editors (ICMJE)

requires all interventional trials (including all phases, surgical,

behavioural and other interventions) to be registered in

ClinicalTrials.gov. All trials must be registered prior to enrollment of

first participant.

3.0 Responsibility: The Case Comprehensive Cancer Center registration coordinator

registers all applicable clinical trials and reports results.

4.0 Definitions:

4.1 Applicable clinical trials: Trials of Drugs and Biologics: Controlled,

clinical investigations, other than Phase I investigations, of a product

subject to FDA regulation; Trials of Devices: Controlled trials with

health outcomes of a product subject to FDA regulation (other than

small feasibility trials) and pediatric post-market surveillance trials.

4.2 Registration Coordinator: Person(s) responsible for registering and

maintaining trials.


2

4.3 Sponsor: Initiator and owner of the study data, grant recipient, IND

holder (if applicable).

4.4 CTRP: The National Cancer Institute Clinical Trials Reporting Program

[Refer to SOP TR-4.1.0, National Cancer Institute Clinical Trials

Reporting Program (CTRP)]

4.5 OnCore® Clinical Trials Management System (referred to as OnCore):

Database to track information from clinical trials conducted by the Case

CCC.


5.0 Procedure The Case CCC maintains a central office with a registration coordinator

responsible for registering and maintaining trials within the Case CCC

ClinicalTrials.gov account.

5.1 Interventional Treatment Trials: To be compliant with FDAAA and

ICMJE regulations, all interventional clinical trials are registered after

approval by the Protocol Review and Monitoring Committee (PRMC). A

PDF file is sent to the PI for approval of the information. (See

ClinicalTrials.gov website for required data elements.)

5.1.1 IND trials: If the PI is the IND holder, then he/she is the

responsible party. The registration coordinator will set up an account in

clinicaltrials.gov for the PI to approve and release the study.

5.1.2 Once the protocol is approved and “released,” personnel at

ClinicalTrials.gov will review and post comments on the Case CCC

account at ClinicalTrials.gov. Corrections can be made, as needed, and the

trial can be re-released. If there are no review comments the trial is

released to the public website within 2 business days.

5.2 Maintenance: Per FDA regulations, trials must be updated every six

months. Clinicaltrials.gov notifies the registration coordinator’s account of

which trials are due for updates. Changes are made on an ongoing basis as

the registration coordinator gets notifications of amendment and status

updates.

5.3 Results reporting: see SOP#: TR-4.3.0: Clinical Trials Results Reporting

with ClinicalTrials.gov

6.0 Penalties for non-compliance 6.1 Up to $10,000 per day fine for unreported results

6.2 Withholding of NIH grant funding

6.3 ICMJE may refuse to publish work associated with the trial

7.0 References https://sreportal.case.edu (Gateway to Case CCC database for clinical trials)

https://register.clinicaltrials.gov (ClinicalTrials.gov registration site)

http://prsinfo.clinicaltrials.gov/s801-fact-sheet.pdf (public law info)

http://clinicaltrials.gov (ClinicalTrials.gov public website)

http://prsinfo.clinicaltrials.gov/definitions.html (data element definitions)

https://trials.nci.nih.gov (NCI-CTRP registration site)

http://www.cancer.gov/clinicaltrials (NCI public website)


https://register.clinicaltrials.gov/

http://prsinfo.clinicaltrials.gov/s801-fact-sheet.pdf


http://prsinfo.clinicaltrials.gov/definitions.html





1

Title: Clinical Trials Results Reporting with ClinicalTrials.gov

SOP #: TR-4.3.0

Version #: 4.0


Effective Date:

December 6, 2012

Revision Dates:

February 3, 2014

April 7, 2015

June 21, 2017


To document the process for reporting clinical trial results with ClinicalTrials.gov.

2.0 Scope: The U.S. Food and Drug Administration (FDA) is the government agency

that requires registration and results reporting of clinical trials. The

ClinicalTrials.gov website is maintained by the National Library of Medicine

(NLM) at the National Institutes of Health (NIH)

2.1 ClinicalTrials.gov: The Food and Drug Administration Amendments Act of

2007 (FDAAA or US Public Law 110-85) passed on September 27, 2007

requires mandatory registration and results reporting for certain clinical trials

of drugs, biologics, and devices. Results are required for all phases other than

Phase I and small feasibility trials.

2.2 Case Comprehensive Cancer Center (Case CCC) is required to register

applicable clinical trials within 21 days of a trial activation or “opening to

accrual”. Results from the clinical trials must be registered within 1 year of

completing data collection for the pre-specified primary outcome. The

purpose of this law is intended to facilitate enrolment in clinical trials, allow

for tracking of the progress of such trials and address problems with the lack

of timely dissemination of research findings.

2.3 All NIH funded interventional trials, regardless of phase, must report results

within 1 year of completing data collection for the pre-specified primary

outcome or risk loss of funding.

3.0 Responsibility The Case CCC registration coordinator registers all applicable clinical trials and

reports results.

4.0 Definitions

4.1 Applicable Clinical Trials: Trials of Drugs and Biologics: Controlled, clinical

investigations, other than Phase I investigations, of a product subject to FDA

regulation; Trials of Devices: Controlled trials with health outcomes of a

product subject to FDA regulation (other than small feasibility trials) and

pediatric postmarket surveillance trials. CTRP: The National Cancer Institute

Clinical Trials Reporting Program [Refer to SOP TR-4.1.0, National Cancer

Institute Clinical Trials Reporting Program (CTRP)].


2

4.2 Registration Coordinator: Person(s) responsible for registering and

maintaining trials. The registration coordinator is also an administrator of the

Case CCC ClinicalTrials.gov account.

4.3 Sponsor: Initiator and owner of the study data, grant recipient, IND holder (if

applicable).

4.4 OnCore® Clinical Trials Management System (referred to as OnCore):

Database to track information from clinical trials conducted by the Case CCC.


5.0 Procedure The Case CCC maintains a central office with a registration coordinator

responsible for results reporting with ClinicalTrials.gov.

Information for results reporting comes from the Principal Investigator,

statistician(s) and the OnCore database. It is critical that data in OnCore are

maintained and updated on an on-going basis by PIs and study staff.

5.1 The primary completion date (PCD) determines the time frame for results

reporting. The primary completion date is the date when the final subject was

examined and/or received an intervention for the purposes of final collection

of data for the pre-specified primary outcome (as per protocol), regardless

whether the clinical trial was completed or terminated. The sponsor has one

year from this date to enter trial results.

5.1.1 Patient status dates and primary outcome time frame determines

the primary completion date.

5.1.2 The registration coordinator receives notification once a study is

closed to accrual. The registration coordinator will then monitor

the patient status (on treatment, off treatment, off study) to

determine the PCD. This date can be entered in

ClinicalTrials.gov as “anticipated” and updated as the study

moves forward. Once the date is set as “actual” then the sponsor

has 1 year from this date to enter results.

5.1.3 The primary completion date field is updated in OnCore by the

registration coordinator.

5.1.4 The registration coordinator will contact the PI and study team to

confirm the primary completion dates.

5.2 Results Modules: there are five modules of data required.

5.2.1 Participant Flow: Description of the number of research

participants starting and completing the study, including

exclusions and dropouts, for each arm or comparison group

5.2.2 Baseline Characteristics: Demographic and baseline data for the

study population and each arm or comparison group

5.2.3 Outcome Measures and Statistical Analyses: Table of outcome

measure values for each arm or comparison group, including

appropriate statistical analyses. For all pre-specified primary and

secondary outcome measures: name and description; unit of


3

measurement; time frame; analysis population; and summary

data, total and by arm.

5.2.4 Adverse Events: Number and frequency of all serious adverse

events and other adverse events exceeding a specified frequency

threshold in each arm or comparison group, grouped by organ

system.

5.2.5 Documents: The final protocol and statistical analysis plan is

required at the time results are submitted. The protocol must

include the official title, NCT number, version date, and

summary table of all global IRB amendments. If a statistical

analysis plan is not included in the protocol, it must be submitted

separately. Study names, addresses, and other personally

identifiable information may be redacted from the document.

5.3 Process for clinical trials results registration.

5.3.1 The registration coordinator will contact the study data manager

prior to entering results to confirm that all data has been entered

into the OnCore system

5.3.2 The registration coordinator will enter applicable information on

a template from the OnCore database, using the DSMC and

Biostats Consoles (Appendix I).

5.3.3 The registration coordinator will send the template to the PI and

study team requesting additional required information. The

competed template is returned to the registration coordinator for

reporting results in ClinicalTrials.gov.

5.3.2 If necessary the PI, statistician and/or study staff will be

contacted to discuss clarifications. Please note that for trials with

already published manuscripts, while the manuscripts are useful,

they do not replace the template.

5.3.3 After all the data are entered in ClinicalTrials.gov and reviewed

and verified by the PI and statistician, the information can be

formally submitted (released). IND trials must be released by the

PI.

5.3.4 ClinicalTrials.gov will review the submission and post comments

for corrections/clarifications. Depending on the nature of

corrections, these can be done by the registration coordinator

and/or PI, as necessary. Once the review process is complete,

ClinicalTrials.gov will send notification to the registration

coordinator (and to PI, if PI is an IND holder) that the submission

of study results has been approved and will be published on the

ClinicalTrials.gov website within 2 business days.

5.3.5 Secondary outcome results, if not reported at initial results

submission, are reported when data have been analyzed and

tabulated. Anticipated posting dates must be included at the time

of primary outcome results entry. The PI and statistician are

responsible for communicating this information to the

registration coordinator.

https://oncore.cwru.edu/

https://register.clinicaltrials.gov/


http://prsinfo.clinicaltrials.gov/s801-fact-sheet.pdf

http://prsinfo.clinicaltrials.gov/results_definitions.html





5

APPENDIX I

CTGOV Results Reporting Template

CASE XXXX: Title/PI

Participant Flow: Description of the number of research participants starting

and completing the study, including exclusions and dropouts, for each arm or comparison group (frequently reported as a CONSORT diagram in a journal article) and for each period/milestone. Period(s) * Definition: Discrete stages or interval of trial activity of a clinical trial during which numbers of participants at specific significant events or points of time are reported. If only one period, use Overall Study for "Period Title." Example of two periods: sertraline then placebo; placebo then sertraline; double blind then open blind. (Time Change) Milestone(s) * Definition: Specific events or time points in the trial when the numbers of participants are reported. While there is no limit to the number of milestones that may be used in a single period, data are required for two milestones, STARTED and COMPLETED, within each period. (Population Change)

ARM/GROUP 1

ARM/GROUP 2

START

Period/milestone

COMPLETED

Reason not completed

ADVERSE EVENT

WITHDRAWAL by SUBJECT

DEATH

LACK of EFFICACY

LOST to FOLLOW-UP

PHYSICIAN DECISION

PREGNANCY

PROTOCOL VIOLATION

OTHER (EXPLAIN)


6

Baseline characteristics: Demographic and baseline data for the study

population and each arm or comparison group (frequently reported as “Table 1” in a journal article). Study-Specific Baseline Measure: clinical measures relevant to the study

Clinical characteristics, including baseline values of outcome measures

Prior and concurrent treatment characteristics

AGE ARM/GROUP 1

ARM/GROUP 2

Continuous (Mean +/-SD)

20-29

30-39

40-49

50-59

60-69

70-79

80-89

GENDER

Female

Male

RACE

American Indian or Alaska Native

Asian

Native Hawaiian or Other Pacific Islander

Black or African American

White

More than one race

Unknown or Not Reported

ETHNICITY

Hispanic or Latino

Not Hispanic or Latino

Unknown or Not Reported

STUDY SPECIFIC BASELINE MEASURE (title, unit of measure, measure type*, dispersion/precision


7

type*)

*Measure Type: *Measure of Dispersion: Number Not Applicable Mean Standard Deviation Median Inter-Quartile Range Least Squares Mean Full Range Geometric Mean Log Mean


8

Outcome Measures and Statistical Analyses: Table of outcome

measure values for each arm/comparison group, including appropriate statistical analyses. For all pre-specified primary and secondary outcome measures: name and description; unit of measurement; time frame; analysis population; and summary data, total and by arm. Analysis Population Description: Definition: Explanation of how the number of participants for analysis was determined. Indicate whether the analysis was "per protocol", "intention to treat (ITT)", or another method.

PRIMARY OUTCOME

Time Frame

Analysis Population Description

No. Participants Analyzed

MEASURE (title, unit of measure, measure type*, dispersion/precision type*)

ARM/GROUP 1

ARM/GROUP 1

Statistical Analysis (provide only one): P value, Confidence Interval OR Estimated Value

P value Method

Confidence Interval Number sides Lower limit Upper limit Parameter Dispersion Type

Estimated Value Parameter


9

SECONDARY OUTCOME

Time Frame

Analysis Population Description

No. Participants Analyzed

MEASURE (title, unit of measure, measure type*, dispersion/precision type*)

ARM/GROUP 1 ARM/GROUP 2

Statistical Analysis (provide only one): P value, Confidence Interval OR Estimated Value

P value Method

Confidence Interval Number sides Lower limit Upper limit Parameter Dispersion Type

Estimated Value Parameter

*Measure Type: *Measure of Dispersion: Number Not Applicable Mean Standard Deviation Median Inter-Quartile Range Least Squares Mean Full Range Geometric Mean Log Mean


10

ADVERSE EVENT DATA WILL BE EXTRACTED FROM ONCORE Time Frame for Adverse Event Reporting: Period in which the reported adverse event data were collected (e.g., 1 year, 6 months) Serious Adverse Events include adverse events that result in death, require either inpatient hospitalization or the prolongation of hospitalization, are life-threatening, result in a persistent or significant disability/incapacity or result in a congenital anomaly/birth defect. Other important medical events, based upon appropriate medical judgment, may also be considered Serious Adverse Events if a trial participant's health is at risk and intervention is required to prevent an outcome mentioned. Serious Adverse Events: A table of all anticipated and unanticipated serious adverse events, grouped by organ system, with number and frequency of such events in each arm of the clinical trial. Other (Not Including Serious) Adverse Events: A table of anticipated and unanticipated events (not included in the serious adverse event table) that exceed a frequency threshold within any arm of the clinical trial, grouped by organ system, with number and frequency of such events in each arm of the clinical trial. Other (Not Including Serious) Adverse Events are those that are not Serious Adverse Events that exceed a frequency threshold. Frequency Threshold for Reporting Adverse Events: Overall number of participants affected by one or more Other (Not Including Serious) Adverse Events above the specified Frequency Threshold (e.g., 5%) reported in the table.

COMMENTS/QUESTIONS:


SECTION 5: PROJECT MANAGEMENT (PM)


1

Title: Responsibilities of the Lead Institution for Joint Cancer-Related Research

Studies SOP #: PM-5.2.0 Version #: 1.0 Original Approval Date: May 3, 2011

Effective Date:

July 3, 2011

Revision Dates:


To document the process for determining the lead institution for joint research studies and to outline the responsibilities of the lead institution.

2.0 Scope All cancer-related research studies.

3.0 Responsibility Principal Investigator; Regulatory Managers; Regulatory Coordinators.

4.0 Definitions: None

5.0 Procedure

All cancer-related research studies are subject to oversight by the Case Comprehensive Cancer Center (Case CCC). The Case CCC is comprised of three institutions, University Hospitals, Cleveland Clinic and Case Western Reserve University. There are two clinical institutions, Cleveland Clinic and University Hospitals. These institutions are expected to work jointly, and one institution will be considered the lead institution for each trial.

5.1 All cancer-related research studies must be reviewed by the Protocol Review and

Monitoring Committee (PRMC) and the Case Cancer Institutional Review Board (Case Cancer IRB).

5.2 The institution that initiates the review process is called the “lead institution” and is responsible for communicating activity to the other institution.

5.3 The lead institution must identify if the other institution would like to participate and clarify with the sponsor if the additional institution is permitted to participate. If yes, the following steps are the responsibility of the lead institution:

5.3.1 Notify the PRMC (and subsequently the Case Cancer IRB) of the institution’s planned participation.

5.3.2 Notify the other institution that they are permitted to participate and relay sponsor contact information.

5.3.3 It is the responsibility of the non-lead institution to contact the sponsor to initiate their start-up process.

5.4 The lead institution is responsible for securing PRMC approval and subsequently submitting the study to the Case Cancer IRB.


2

5.5 The lead institution must notify the sponsor to distribute study materials (e.g. regulatory binders, lab manuals, kits, etc.) to each institution separately.

5.6 All internal Serious Adverse Events (SAEs) and internal protocol deviations are

to be processed and submitted to the Case Cancer IRB and the Data Safety and Toxicity Committee (DSTC) by the institution where the SAE/protocol deviation occurred. SAEs and deviations are entered into OnCore. A copy of the IRB submission must be sent to the other institution (all SAEs should be shared with both institutions; the lead institution should have a copy of all deviations).

5.7 It is the responsibility of the lead institution to keep OnCore updated, including the institution, management, status and IRB submission screens. Documents should be attached for IRB submission, the protocol, and IRB approved, stamped consent(s).

5.8 Each site is responsible for entering and updating each of their patient’s demographics, consent, eligibility, on/off study date, sequence number, on/off treatment (as applicable), follow-up fields, SAEs and protocol deviations in OnCore.

5.9 The lead institution is responsible for submitting all protocol amendments to the Case Cancer IRB (and PRMC if appropriate). A copy of the Case Cancer IRB submission must be distributed to the other participating institution. The paperwork to add or remove study staff should be completed by the site adding/removing the staff. The paperwork is then sent to the lead site for submission to the IRB. The lead site is responsible for updating the Protocol Staff on the Management screen in OnCore upon IRB approval.

5.10 The lead institution is responsible for submitting all continuing reviews to the Case Cancer IRB. It is the responsibility of the non-lead institution to provide all relevant data to the lead institution in a timely manner. A copy of the IRB submission must be distributed to the other participating institution. This can be accomplished by attaching the document in OnCore with the Document Type IRB Approval Letter and notify via email the opposite institution.

5.11 The lead institution is responsible for processing IRB defined external SAEs. 5.12 Internal processing of external safety letters is per institutional policy;

however, only the lead institution will submit external safety letters to the IRB and/or DSTC. If external safety letters meet IRB reporting guidelines, a copy of the IRB submission must be distributed to the other participating institution. If immediate action is required for an external safety letter, the lead institution is responsible for submission to the DSTC and for notifying any participating sites that were not already notified by the sponsor.

Should the lead site decide to terminate their participation in a joint study, they should follow the SOP PM-5.1.0, Transfer of the Lead Institution Responsibilities to the Secondary Institution for Joint Cancer-Related Research Studies.

6.0 References

https://oncore.cwru.edu (OnCore) http://cancer.case.edu/researchadmin/prmc(PRMC instructions and forms-password protected) http://casemed.case.edu/ora/irb/irbpolicy.cfm (Case Cancer IRB SOPs)

7.0 Appendices: None


3


SECTION 6: SUBJECT MANAGEMENT (SM)



1

Title: Verification and Confirmation of Independent Review of Patients’ Responses on

Investigator-Initiated Clinical Trials

SOP #: SM-6.2.0

Version #: 2.0


Effective Date:

November 21, 2013

Revision Dates:

December 5, 2016


To outline the process for confirmation of responses for Case Comprehensive Cancer

Center (Case CCC) investigator-initiated trials (IITs).

The process of reviewing sets of comparative measurements is an essential Quality

Assurance (QA) function of an academic medical center. In NCI-designated Cancer

Centers, the data safety oversight is performed on all investigator-initiated clinical trials

by the Data Safety and Toxicity Committee (DSTC).

The DSTC oversight includes the review of the process in which an independent

reviewer(s) confirmed that patients had a response (solid tumor and hematologic

response) following cancer treatment on an investigator-initiated investigational studies.

The DSTC review of the process is critical for: 1) QA; 2) compliance with federal NCI

regulations; and 3) assurance of independent review to avoid conflict of interest and bias.

The written reply from the DSTC regarding its review of the response will follow the

DSTC meeting when the response is presented and discussed. The DSTC will also assist

to facilitate the process for additional reviews in cases when the independent review does

not confirm readings by the Principal Investigator (PI). The PI or the research

coordinator will provide the DSTC with the appropriate imaging and response documents

necessary to complete the response confirmation process.

It is the responsibility of each Principal Investigator to ensure that the process of

independent review takes place and that applicable information and documents are

submitted to the DSTC in a timely fashion.

2.0 Scope

All Case CCC cancer-related IITs.

3.0 Responsibility The Principal Investigator (PI) for each Case CCC cancer-related investigator-initiated

treatment clinical trial.

4.0 Definitions: None.


SECTION 7: DATA SAFETY AND MONITORING COMMITTEE (DSTC)

& DATA SAFETY AND MONITORING (DSM)



1

Title: Submission of Documents to the Data Safety and Toxicity Committee

SOP #: DSTC/DSM-7.1.0

Version #: 1.0

Original Approval Date: September 2, 2014

Effective Date:

November 2, 2014

Revision Dates:


To document the requirements, process, and timeline for submitting objective responses, audit

and monitoring results, continuing reviews, serious adverse events, and major deviations to the

Data Safety and Toxicity Committee and the process and timeline for notification of approval.

2.0 Scope The purpose of the DSTC is to oversee all aspects of data monitoring and safety for

institutionally sponsored, investigator-initiated interventional trials and those trials that do not

have external monitoring that are active at the Case CCC.

3.0 Responsibility It is the responsibility of the committee to review objective responses, audit results, monitoring

results that are questionable or unacceptable, continuing reviews, serious adverse events, and

major deviations in terms of data integrity and patient safety.

4.0 Definitions 4.1 Case CCC: Case Comprehensive Cancer Center

4.2 CR: Continuing Review

4.3 Deviation: Any variation from the protocol requirements

4.4 DSTC: Data Safety and Toxicity Committee

4.5 OnCore™: Clinical Trials Management System (referred to as OnCore): database to

track information from clinical trials conducted by the Case CCC

4.6 PI: Principal Investigator

4.7 SAE: Serious Adverse Event

5.0 Procedures 5.1 All internal SAEs and external SAEs under Investigator-initiated trials purview will be

reviewed on a twice monthly basis at the meeting following their receipt by the DSTC.

5.1.1 SAE submission should include an SAE report per the protocol requirements

with a matching entry in OnCore per the respective IRB reporting

requirements.

5.1.1.1 The DSTC will only review SAEs that occur after initiation of

protocol treatment and fall within the defined SAE parameters

specified in the protocol.

5.2 Major protocol deviations; for example, ineligibility, consent form issues, treatment error

or a treatment that is not within the guidelines of the protocol will be reviewed on a twice

monthly basis at the meeting following their receipt by the DSTC.



2

5.2.1 Submission of major deviations should include a detailed OnCore entry

including an “Action Taken” per the respective IRB reporting requirements.

5.2.2 Deviations deemed to be minor are reviewed by the DSTC at the continuing

review.

5.3 It is strongly recommended that CRs are sent annually to the DSTC for any investigator

initiated trials that have had activity of accrual, had active patients, and/or SAEs during

the reporting time frame at least 30 calendar days prior to submission to the IRB. (Refer

to Case CCC SOP: DSTC/DSM-7.2.0: Submission of Continuing Reviews to the Data

Safety and Toxicity Committee)

5.4 Objective responses (partial and complete responses) of the Case CCC investigator-

initiated trials, and those trials that the physician requests an unbiased review, will be

confirmed based on the criteria for response defined in the protocol. (Refer to Case CCC

SOP: SM-6.2.0: Verification and Confirmation of Independent Review of Patients’

Responses on Investigator-Initiated Clinical Trials)

5.4.1 Responses must be confirmed by the treating MD and an independent

reviewer, and submitted to DSTC to be considered reportable.

5.4.2 Submission of responses should occur as soon as possible after confirmation

of best response.

5.4.2.1 All results will be entered in OnCore into the Review section under

DSMC Action History by each institution’s coordinator.

5.5 All audit reports should be submitted to the DSTC as soon as possible either after the

receipt by PI and study team of an acceptable report from the auditor or after submission

of response and corrective action plan to the auditor.

5.6 Other items requiring prompt submission to the DSTC include protocol specific special

safety reviews, safety concerns and issues referred by either PRMC or monitoring

committees for high risk clinical trials, and internal SAEs on behavioral trials and should

be forwarded to the DSTC site coordinator within 14 calendar days of submission to the

respective IRB.

5.7 Following submission of any of the aforementioned materials, the DSTC will notify the

PI with a copy to any appropriate parties, such as regulatory specialist, research nurse

specialist, etc. of confirmation, denial, or questions regarding material submission within

7 calendar days of the DSTC meeting and review.

5.7.1 The DSTC reserves the right to request, as appropriate, changes in the consent

form to inform patients of previously unrecognized risks, changes in dose

modifications, schedules or toxicity monitoring.

5.8 Any delinquency in submission or receipt of the aforementioned materials will be

directed to the Administrative Director of the Case CCC Clinical Research Office.

6.0 References Case CCC Data and Safety Monitoring Plan

7.0 Appendices None



1

Title: Submission of Continuing Reviews to the Data Safety and Toxicity Committee

SOP #: DSTC/DSM - 7.2.0

Version #: 1.0


Effective Date:

November 2, 2014

Revision Dates:


To document the requirements, process, and timeline for submitting continuing reviews to

the Data Safety and Toxicity Committee and the process and timeline for notification of

approval.

2.0 Scope The DSTC receives IRB continuing review reports for treatment investigator-initiated

trials—interventional trials that are open to accrual or those that have been open and closed

to accrual with the 1 year timeframe reported—that have had activity of accrual, had active

patients, deviations and/or SAEs.

3.0 Responsibility It is the responsibility of the committee to review accrual goals, toxicity, response, study

conduct to ensure data integrity, and safety. The DSTC determines whether an early

stopping toxicity endpoint has been met and whether protocol and consent form

modifications are needed.


4.2 CR: Continuing Review

4.3 CRO: Clinical Research Office

4.4 CTO: Clinical Trials Office

4.5 Deviation: Any variation from the protocol requirements

4.6 DSMC: Data Safety and Monitoring Coordinator (OnCore role)


4.8 IRB: Institutional Review Board

4.9 OnCore™: Clinical Trials Management System (referred to as OnCore): database

to track information from clinical trials conducted by the Case CCC

4.10 PI: Principal investigator

4.11 SAE: Serious adverse event

5.0 Procedures 5.1 It is strongly recommended that continuing reviews are sent annually to the DSTC

for any investigator initiated trials that have had activity of accrual, had active

patients, and/or SAEs during the reporting time frame at least 30 calendar days

prior to submission to the IRB.

5.2 The continuing review form should include the following information:



2

5.2.1.1 Study objectives

5.2.1.2 Accrual goals and current enrollment status

5.2.1.3 Enrolled patient status, including Off-Treatment and Off-Study

reasons

5.2.1.4 Reconciliation of SAE reports and Deviation reports submitted

to the IRB and the DSTC

5.2.1.5 Clinical responses—only those that have been previously

confirmed by the DSTC

5.3 Continuing reviews will be submitted to the DSTC coordinator prior to the twice

monthly DSTC meetings and will be reviewed at the committee’s next scheduled

meeting.

5.3.1 Approval, disapproval, or questions from the committee will be

communicated within 7 calendar days to the PI, the regulatory specialist,

and any involved parties to await reply. A reply from the PI, if

applicable, is requested within 14 calendar days. A lack of response

from the PI will result in an escalation of the issue to the Associate

Director for Clinical Research and the CTO Medical Director for the

Case CCC. (Refer to Case CCC SOP: DSTC/DSM-7.3.0: Data Safety

and Toxicity Committee Reporting and Communicating Action Items)

5.3.1.1 All results will be entered in OnCore into the Review section

under DSMC Action History by each institution’s coordinator.

5.4 In rare circumstances, the DSTC can review CRs and render its decision via email

between twice monthly meetings. If a CR is submitted less than 30 days before

IRB submission, prior approval from the DSTC Chair must first be obtained by the

PI.

5.5 Reasons for protocol suspension, closure to accrual or termination may include, but

are not limited to, the following:

5.5.1 accrual goal met;

5.5.2 stopping rules activated due to:

5.5.2.1 the dose escalation has reached the dose limiting toxicity or the

maximum tolerated dose, as indicated by the protocol,

5.5.2.2 excessive toxicity and/or,

5.5.2.3 interim analysis of two-stage design indicates a response above

or below the margins outlined in the trial;

5.5.3 deviation rate deficient and/or correction action not effective;

5.5.4 DSTC has concerns about protocol conduct or ability of the PI to

continue to meet local or federal regulations.

6.0 References Case CCC Data and Safety Monitoring Plan.

7.0 Appendices None



1

Title: Data Safety and Toxicity Committee Reporting and Communicating Action

Items

SOP #: DSTC/DSM-7.3.0

Version #: 1.0


Effective Date:

November 2, 2014

Revision Dates:


To document the process for reporting and communicating Data Safety and Toxicity

Committee action items to all necessary parties, including the PI, IRB, PRMC, Associate

Director for Clinical Research, and CTO Medical Director.

2.0 Scope The DSTC is an independent committee that communicates its actions, such as immediate

administrative hold, suspension of enrollment, or study termination to the PI, IRB,

PRMC, Associate Director for Clinical Research, and CTO Medical Director.

3.0 Responsibility It is the responsibility of the DSTC chair to report and communicate the committee’s

actions to all applicable parties. It is the PI responsibility (with support of the CTU or

CRO) to communicate the DSTC actions to the study sponsor and other oversight

agencies, as applicable and /or as dictated by a particular protocol.


4.2 CCF: Cleveland Clinic Foundation

4.3 CRO: Clinical Research Office

4.4 CTO: Clinical Trials Office

4.5 CTU: Clinical Trials Unit


4.7 IRB: Institutional Review Board

4.8 PI: Primary Investigator

4.9 PRMC: Protocol Review and Monitoring Committee

4.10 SCC: Seidman Cancer Center

4.11 TCI: Taussig Cancer Institute

4.12 UH: University Hospitals

5.0 Procedures 5.1 Action items identified at DSTC meetings—including but not limited to:

administrative hold, suspension of enrollment, or study termination—will be

detailed within the meeting minutes and individual notice will be sent to involved

parties.


SECTION 8: AUDITING AND MONITORING [QUALITY ASSURANCE] (QA)

Appendix I

Version 2.0; 5/5/2015 SOP Number: QA-8.1.0; Monitoring Investigator-Initiated Clinical Trials Appendix I: Monitoring Training Checklist

Monitoring Training Checklist

This checklist with appropriate documentation will be maintained in departmental files. The

designated management personnel will verify that the information on this form is complete and

that the staff is prepared to monitor.

Name of Monitor: _____________________________________________

Date of Hire: ___________________

Requirements

Document Name Yes or No

Current Curriculum Vitae that demonstrates two or more years of clinical research experience

Copy of quality assurance course (including certificate of completion, agenda) on file

Documentation of at least two site monitoring training visits with a trained and more experienced site monitor or minimum of six months hands-on monitoring experience/assessment of regulatory compliance

Review of Institutional Policy

Review of CCCC Monitoring of Clinical Investigations SOP

Review of CCCC Clinical Trials Manual of Operations

Review of ICH E6 Good Clinical Practice Guidelines

Review of Federal Code of Regulations Title 21 Part 11, 50, 54, 56, 312, 812 Guidelines for Monitoring of Clinical Investigations (January 1988)

Monitor Signature: _______________________________ Date: ________________________

Appendix II

Version 3.0; 5/5/2015 CONFIDENTIAL SOP Number: QA-8.1.0; Monitoring Investigator-Initiated Clinical Trials Appendix II: Monitoring Plan Template

Monitoring Plan Template

Study Title:

PRMC # and/or IRB #:

Sponsor Investigator:

Sponsor-Investigator Signature: _____________________ Date: _________


Abbreviations AE Adverse Event CFR Code of Federal Regulations eCRF Electronic Case Report Form DSTC Data Safety Toxicity Committee FDA Food and Drug Administration GCP Good Clinical Practice ICF Informed Consent Form ICH-GCP International Conference on Harmonization -Good Clinical Practice IND Investigational New Drug IDE Investigational Device Exemption IRB Institutional Review Board PI Principal Investigator SAE Serious Adverse Event SD Source Documents SDV Source Data Verification SOP Standard Operating Procedures


Table of Contents

1.0 Introduction ................................................................................................ 4 2.0 Monitoring Scope ....................................................................................... 4 2.1 Monitor Primary Responsibilities 2.2 Data Monitoring 2.3 Monitoring Visit Reports 3.0 Initiation Visit .............................................................................................. 6 3.1 Purpose and Scope 3.2 Initiation Visit Monitoring Activities 4.0 Interim Monitoring Visits ............................................................................. 7 4.1 Purpose, Frequency and Scope 4.2 Interim Monitoring Visit Activities 5.0 Electronic Case Report Form Completion and Retrieval ............................ 8 6.0 Drug Accountability .................................................................................... 9 7.0 Close-Out Visit ........................................................................................... 9 7.1 Purpose and Scope 7.2 Closeout Visit Activities


1.0 Introduction This Monitoring Plan should be used as a guide to monitor the progress of clinical trial, [PRMC # and/or IRB #]. The following is a list of the minimum criteria and does not replace an understanding of, or adherence to, the requirements contained in the approved protocol, any possible amendment(s) or numbered memo(s). Monitors will ensure that the clinical trial is conducted, recorded and reported in accordance with the protocol, Code of Federal Regulations (CFR), International Conference on Harmonization-Good Clinical Practice (ICH-GCP), IRB Policies and Procedures, any applicable local regulations, and Case Comprehensive Cancer Center (CCCC) /Institute / Enterprise SOPs, as well as the Sponsor-Investigator’s Standard Operating Procedures (SOP). In the event of a conflict between this document and an SOP, this document supersedes the SOP. 2.0 Monitoring Scope

2.1 Monitor Primary Responsibilities Monitors will review clinical data that affect clinical trial endpoints defined in the protocol. The monitor will compare the practices and procedures of the investigator with the protocol and regulatory applications. The primary responsibilities of the monitor include the following:

Verify investigators have adequate qualifications to safely and properly conduct the trial.

Verify that facilities remain compliant throughout the trial.

Verify storage, dispensing, instructions for use, and disposition of the investigational agent complies with regulatory requirements.

Verify the site follows the approved protocol and deviations are filed for noncompliance as applicable.

Verify that written consent was obtained before subjects’ participation and consent process was completed and documented.

Verify that delegated personnel are informed about the trial and no unauthorized individuals have been delegated responsibilities.

Verify that only eligible subjects are enrolled.

Verify trial records are accurate, complete, and current.

Check the accuracy and completeness of electronic Case Report Form (eCRF) entries, source documents (SD), and other trial-related records against each other.

Inform the investigator(s) of any eCRF errors and ensure corrections are made, dated and explained and initialed by the investigator or designee as applicable.

Determine whether all adverse events (AEs) and serious adverse events (SAEs) are reported.

Determine all regulatory documents are maintained.


Verify all study-related correspondence with the Food and Drug Administration (FDA) related to the IND / IDE (as applicable), Institutional Review Board (IRB), and Data Safety Toxicity Committee (DSTC).

Communicate deviations from the protocol, GCPs or regulatory requirements to the investigator and discuss appropriate action to prevent recurrence of the deviations.

At the end of each monitoring visit, the monitor will meet with the PI and/or delegated personnel to review findings and discuss follow up of the visit.

2.2 Data Monitoring Source Data Verification (SDV) is the process of comparing data recorded on the eCRF to the data contained in the SDs. SDs are defined as any original records or data related to the study or to subject treatment or medical history. SDs may include but not be limited to subject medical history, current hospitalization examinations, chart notes, lab reports, x-rays and electrocardiograms (ECGs). The subject’s record will be screened for relevant data that is not captured in the eCRF (e.g. verifying that no AEs and /or other endpoints are missed).

Verification of the following will be conducted at 100% SDV for all patients:

Initial study consent and the consent process for 100% of enrolled and screened patients;

Study eligibility for 100% of enrolled patients;

SAE/AE reporting for 100% of enrolled patients;

Study drug dosing for 100% of enrolled patients (as applicable). An excessive number of eCRF discrepancies at the site will prompt review of additional subjects and/or data in addition to those planned.

2.3 Monitoring Visit Reports The monitor will complete a monitoring visit letter and monitor visit regulatory binder report for each visit and send to the Sponsor-Investigator and to the PI (if not the same) and/or designated personnel within 10 business days of the conclusion of the monitoring visit. A copy of every monitoring visit letter, monitoring visit regulatory binder report and site specific documentation will be retained by the monitor. The monitor will notify the Sponsor within three business days of the visit of any critical site issues noted during the visit. The monitoring visit report and cover letter will describe the progress of the study, findings of the visits, unresolved issues and follow-up


required. Follow-up items will be checked and documented at the next monitoring visit as applicable. The monitoring visit report will include, but not limited to, the following:

Summary of data and regulatory documents that were reviewed;

Statement that regulatory, pharmacy and data were acceptable, acceptable with follow-up required, unacceptable or not reviewed;

Statement concerning significant findings such as under-reporting of adverse events;

3.0 Initiation Visit

3.1 Purpose and Scope The purpose of the initiation visit is to conduct and document the training of the PI and delegated personnel in the written approved protocol, verify that the PI and delegated personnel clearly understand and accept their obligations in undertaking the clinical trial, understand all required data, eCRF completion and associated activities necessary to conduct [PRMC # and/or IRB #] in accordance with the federal regulations and ICH-GCP.

The Initiation Visit will occur after IRB approval, but prior to opening the trial to accrual.

3.2 Initiation Visit Monitoring Activities Monitoring activities will include, but not be limited to, discussions related to PI and delegated personnel responsibilities during the conduct of the trial, inclusion/exclusion criteria, definitions of AE/SAE, AE/SAE reporting procedures, regulatory obligations, appropriate use of the investigational drug/device, [study drug/device], and its accountability and destruction/return, the informed consent process, and CRF completion instructions. A tour of the facility may also be requested to ensure it is adequate to conduct the study. This may include, but not be limited to, the emergency department, study drug/device storage area, monitoring areas; CRF and study supply storage areas. Prior to opening this study to accrual the monitor will perform the following tasks:

Regulatory specific study start up monitoring (all regulatory documents will be reviewed to ensure the study start-up documentation meets the following minimal requirements):

PRMC Approval

IRB Approval

FDA submission (may proceed or 30 day period without notification from the FDA)

Regulatory File Review


Regulatory ONCORE specifics

Verify current protocol, IRB approval letter, and consent are uploaded into the documents / information tab

Verify Status / Institution tabs are updated

Verify that the Details, Management, Sponsor, IND/IDE tabs (PC Console) are correct and updated

Verify that correct approved consent information has been entered in the IRB Reviews section

4.0 Interim Monitoring Visits

4.1 Purpose, Frequency and Scope The primary goal of the interim monitoring visit is to assure the study is conducted in compliance with the currently approved protocol, federal regulations, ICH-GCP, ensure subject safety, and validate clinical data against source documents. The monitor will review previous monitoring reports to identify any unresolved issues and discuss with the team during the interim visit. The first interim monitoring visit will occur as soon as possible after the first subject is enrolled. Thereafter interim monitoring visits will occur every 4-6 weeks during the conduct of the trial.

Additional monitoring visits could be triggered by sponsor-investigator request, unexpected enrollment rates, unacceptable number of queries and/or protocol violations or non-compliance with GCPs, and/or complexity of the trial. These visits are to occur within 10 business days of notification to the monitor.

4.2 Interim Monitoring Activities

The following minimum activities will be completed during interim monitoring visits:

Data monitoring to occur as outlined in Section 2.2;

Verify protocol compliance and note any issues for follow-up with the site;

Verify appropriate drug/device accountability; drug/device storage and handling including review of the drug accountability forms and temperature log completion as outlined in Section 6.0;

Review the Subject Identification, Enrollment and Screening Logs; and

Facilitate data query resolution.


Informed Consent Form Process

Verify that the appropriate IRB has approved the Informed Consent Form (ICF) document in use;

Verify that the most recently approved ICF as approved by the IRB was signed and dated by the subject or legal representative, witness and by the PI prior to any study procedure being performed;

Verify all original signed ICFs are filed at the study site and that they are available for review;

Review documentation that all subjects consented have received a copy of the ICF;

Verify that the informed consent process is documented in the SDs and in the study database.

Inclusion/Exclusion Criteria

Verify that all subjects are eligible to participate in the trial based on the protocol's inclusion and exclusion criteria;

Assigned number will be confirmed for all subjects.

Regulatory Documents In addition to monitoring subject data, the monitor will review the regulatory documents for any additions or revisions since the last visit including but not limited to the following:

Verify that any staff changes are reflected on a revised Form FDA 1572/Investigator Agreement, and the Signature and Delegation log are submitted to the IRB;

Verify any changes or amendments to the protocol and/or to the informed consent, any SAEs / deviations are reported to the Sponsor-Investigator, IRB, FDA (SAEs only – if applicable), and DSTC and follow-up occurred;

Verify that the site submits required continuing reviews and reports to the IRB/DSTC, and confirms that IRB approval is current;

Verify the site submits annual report to the FDA (if applicable)

Verify that all training has occurred and training log has been signed for delegated personnel;

Review of site regulatory files and IRB/FDA communication;

5.0 Electronic Case Report Form Completion and Retrieval The data for [PRMC # and/or IRB #] will be captured in ONCORE, the Case Comprehensive Cancer Center’s oncology database. The CRF pages for [PRMC # and/or IRB #] are created and maintained in ONCORE, therefore there are no paper CRF forms. All data will be held in ONCORE and all source documentation will be managed and stored by the research team. The delegated personnel responsible for entering data are required to enter the data per institutional requirements.


eCRF completion timelines will be reviewed according to the institutional requirements. eCRF review will include review for completeness and consistency with source documents. eCRFs should be completed on all subjects that have been screened and enrolled.

6.0 Investigational Agent Accountability The monitor will perform accountability of the investigational agent at each monitoring visit. Verification of the investigational agent includes documenting any discrepancies between the total amounts [study drug/device] shipped to the study site with the total amount of [study drug/device] dispensed to subjects along with unused [study drug/device]. The monitor will verify that correct study drug/device was administered by comparing the medical record against pharmacy documentation. The monitor will perform the following checks and verifications:

Confirm all [study drug/device] was used for each subject and verify dispensed dates;

Check for site pharmacy personnel changes. If changes occur, ensure new personnel will have access to receive the study drug/device during the trial;

Verify that the drug number administered to the subject matches the number assigned for all subjects enrolled;

Review the temperature log. Ensure the temperature is maintained and current.

Ensure that receipt of drug shipments has been acknowledged by the Investigational Pharmacy on Record;

Verify that the test article is stored in a securely locked area. The site staff should not destroy/return study drug/device until the monitor has checked the dispensing records for all subjects against the appropriate documentation (if applicable). 7.0 Close-Out Visit

7.1 Frequency and Scope A close-out visit should occur prior to the termination of the study with the IRB.

7.2 Close-Out Visit Activities

The monitor will perform the following tasks during the study close-out visit:

At the end of the study, the monitor will verify submission of a final report to IRB and FDA (if applicable) and proper close out procedures have been followed;


Facilitate the resolution of outstanding observations/queries;

Perform final [study drug/device] accountability and verify that the [study drug/device] destruction form was completed;

Review regulatory documents;

Review record retention and regulatory responsibilities with the PI and delegated personnel;

Verify all outstanding items from the previous visits have been addressed.

The monitor will remind the PI of his/her obligations regarding study record maintenance and storage according to the applicable FDA and any applicable local regulations.

Appendix III Case Comperehensive Cancer Center

Monitoring Visit Log

Version 2.0; 5/5/2015

SOP Number: QA-8.1.0; Monitoring Investigator-Initiated Clinical Trials Appendix III: Monitoring Visit Log

SOP

Date Type of visit Name of study monitor Signature of study monitor Name of representative of

study personnel Signature of representative of

study personnel

Appendix IV Case Comprehensive Cancer Center

Page 1 of 3 Version 2.0; 5/5/2015 SOP Number: QA-8.1.0; Monitoring Investigator-Initiated Clinical Trials Appendix IV: Monitoring Visit Cover Letter

Monitoring Visit Letter Template [Insert Current Date] Sponsor-Investigator: [Enter Sponsor-Investigator name] Type of Visit: [Enter type of monitoring visit; initiation, interim or close-out] PRMC # and/or IRB #: [Enter PRMC and/or IRB number] IND or IDE #: [Enter IND / IDE number] Protocol Title: [Enter full protocol title] Dear [Insert PI name], On [insert dates of monitoring visit], I conducted a [insert type of monitoring visit] monitoring visit on the above referenced project. Attached is the monitoring visit regulatory binder report for [study number], which should be filed in the regulatory binder in lieu of this letter. The purpose of my review of this area was to determine compliance with the protocol, federal regulations, IRB policies and procedures, ICH-GCP requirements and Case CCC/ institutional / Enterprise SOPs. The results and areas reviewed during my visit are as follows: Regulatory Documents The documents reviewed included: [list documents reviewed if a detailed report is not attached]. My review confirmed that you [are complying or have complied (if close-out)] with all required review requirements. Therefore this study has earned an acceptable rating for this section.

OR My review confirmed that you are complying or have complied (if close-out) with all required review requirements with the following exception(s):

Finding/Concern [State nature of finding/concern and the corrective/recommended action if required]

Due to these findings, this study has earned an [acceptable with follow-up or unacceptable] for this section. Investigational Agent Accountability and Pharmacy Operations The documents reviewed included: [list documents reviewed if a detailed report is not attached]. My review confirmed that you [are complying or have complied (if close-out)] with all required review requirements. Therefore this study has earned an acceptable rating for this section.



OR My review confirmed that you are complying or have complied (if close-out) with all required review requirements with the following exception(s):


Due to these findings, this study has earned an [acceptable with follow-up or unacceptable] for this section. Subject Records Review The target accrual rate for this study is [enter the target accrual rate as provided to IRB] subjects. At the time of this visit, [enter the current accrual rate] subjects were enrolled onto the study. The subjects and documents reviewed include: [list subject numbers and documents reviewed]. My review confirmed that you [are complying or have complied (if close-out)] with all required review requirements. Therefore this study has earned an acceptable rating for this section.

OR My review confirmed that you are complying or have complied (if close-out) with all required review requirements with the following exception(s).


Due to these findings, this study has earned an [acceptable with follow-up or unacceptable] for this section. Summary Based on my monitoring review, [PRMC # and/or IRB #] is proceeding in a timely manner and is being administered in compliance with applicable requirements. I will schedule a [insert type of visit] for [insert date or timeframe known for next visit].

OR Based on my monitoring review, [PRMC # and/or IRB #] is proceeding in a timely manner and is being administered in compliance with applicable requirements, with the exception of the areas previously noted. I will schedule a [insert type of visit] for [insert date or timeframe known for next visit]. You are reminded that the findings listed above must be addressed by [insert date].

OR Based on my monitoring review, [PRMC # and/or IRB #] was administered in compliance with applicable requirements. The project is hereby closed pending receipt



and approval of the outstanding findings identified above. These findings must be addressed by [insert date] in order to close the study with the IRB. Thank you for your assistance and cooperation extended to me during the visit. Should you have any questions or require additional information, please feel free to contact me at [enter monitor’s phone number]. Sincerely, [Name, Title of Monitor and Site Name] Cc: [enter as appropriate; should include Sponsor-Investigator and/or designated personnel, Quality Assurance Manager, Manager of Research Personnel]

Appendix V


Page 1 of 3

Version 2.0; 5/5/2015 SOP Number: QA-8.1.0; Monitoring Investigator-Initiated Clinical Trials

Appendix V: Monitoring Report

Adapted from NCI DCP Template

Monitoring Visit Regulatory Binder Report Template

I. General Information Sponsor-Investigator

Lead Clinical Site UH CC Other ______________

Investigator

Site Monitored UH CC Other ______________

Protocol Title

IND or IDE #

Protocol Target Accrual Enrollment to Date _____

Visit Conducted By

Date(s) of Visit __/__/____ to __/__/____

Type of Visit (check all that apply) Study Initiation Unscheduled

Interim Monitoring Close Out

Study Status Open to Accrual Suspended

Closed to Accrual Terminated

Summary of Documents Reviewed

Date of Next Visit:

Instructions: For the following categories, indicate the assessment for each of the three

components of the monitoring visit.

II. Assessing Regulatory Documents, IRB and Informed Consent Findings Check one

that applies

Rating

Explanation of Rating

Acceptable

No deficiencies identified.

Few minor deficiencies identified.

Major deficiencies identified during the site visit

that were addressed and/or corrected prior to the

site visit for which documentation exists and no

further action is required.

Acceptable, Follow-up

Multiple minor deficiencies identified.

Major deficiencies identified during the site visit,

but not corrected and/or addressed prior to the site

visit.

Unacceptable

Multiple major deficiencies identified.

A single major flagrant deficiency found.

Excessive number of minor deficiencies found.

Not reviewed

Additional Comments:

Appendix V


Page 2 of 3




III. Assessing the Accountability of Investigational Agent and Pharmacy

Operations Check one

that applies

Rating Explanation of Rating

Acceptable

Compliance found for security, drug accountability

record forms completed correctly, protocol and

drug-specific usage and/or return of study drug.

Noncompliant items identified during the site visit

that were addressed and/or corrected prior to the

site visit for which documentation exists and no

further action is required.


Category found noncompliant during the site visit

which was not corrected and/or addressed prior to

the site visit.

Unacceptable

Inability to track the disposition of the supplied

investigational agent.

Multiple noncompliant categories identified.

Not reviewed


IV. Review of Subject Records Check

one that

applies

Rating Explanation of Rating

Acceptable

No deficiencies identified.

Few minor deficiencies identified.

Major deficiencies identified during the site

visit that were addressed and/or corrected prior

to the site visit for which documentation exists

and no further action is required.


Multiple minor deficiencies identified.

Major deficiencies identified during the site

visit, but not corrected and/or addressed prior to

the site visit.

Unacceptable

Multiple major deficiencies identified.

A single major flagrant deficiency found.

Excessive number of minor deficiencies found.

Not reviewed


Action Items Identified:

Additional Comments/General Impressions of Site Performance/ Recommendations:

Appendix V


Page 3 of 3




Prepared by: Title:

Signature: _____________________________________________ Date: ________


SECTION 9: REGULATORY AFFAIRS (RA)



1

Title: Statement of Investigator (Form FDA 1572)

SOP #: RA-9.1.0

Version #: 2.0


Effective Date:

July 3, 2011

Revision Dates:

October 4, 2016


To assist in accurate completion of a protocol specific FDA Form 1572 required for

studies being conducted by the investigator for pharmaceutical or governmental agencies.

2.0 Scope

2.1 All FDA regulated studies conducted under the Investigational New Drug

Application (IND) and managed within the Case Comprehensive Cancer Center

(Case CCC) require Form FDA 1572.

2.2 National Cancer Institute (NCI) cooperative group studies: NCI does not require

the Form FDA 1572 for each protocol. NCI guidelines for registration of all

investigators, which include an annual 1572 (among other documents) per

investigator, must be followed. Industry sponsors may also require a 1572 for

select NCI trials.

3.0 Responsibility Principal Investigator; Regulatory Coordinator; Study Coordinator; Research Nurse.


5.0 Procedure 5.1 Definition and Responsibilities

5.1.1 The FDA Form 1572 is the Investigators ‘Statement’ and ‘Agreement’

to follow the protocol and the federal regulations.

5.1.2 The Principal Investigator (PI) is responsible for the contents of the

1572 and the subsequent study.

5.1.3 The PI or designee completes the form and files in the trial master file.

5.1.4 Each Case CCC Institution must complete separate 1572 forms. For

investigator-initiated studies, the designated lead Institution must

maintain copies of 1572s from all participating sites.

5.2 Form Location

5.2.1 The current version of FDA Form 1572 is located on the FDA website

at: http://www.fda.gov/opacom/morechoices/fdaforms/cder.html

5.3 Initial Form Completion

http://www.fda.gov/opacom/morechoices/fdaforms/cder.html



2

5.3.1 Section 1: The investigator is the individual at the site who both

initiates and conducts the clinical trial and under whose immediate

direction the investigational drug is being administered or dispensed.

5.3.2 Section 2: The box marked curriculum vitae (CV) must be checked.

5.3.2.1 A copy of the principal investigator’s CV must be on file.

5.3.3 Section 3: The address to which written correspondence from the FDA

should be directed.

5.3.4 Section 4: List all clinical labs that will be utilized for the study,

including central and sponsor laboratories as applicable.

5.3.4.1 For example, include a lab within the Case CCC Institutions

if they provide results for the study. Not required to be

added if the lab is only preparing send-outs to an external

laboratory.

5.3.5 Section 5: List the IRB address as appropriate

5.3.6 Section 6: List all sub-investigators for the study.

5.3.6.1 A sub-investigator is defined as anyone who makes a direct

and significant contribution to the data.

5.3.6.2 If a research staff is performing a critical study function and

collecting and evaluating study data the staff should be

listed as a sub-investigator. If the research staff is only

transcribing study data and maintaining study files (e.g.

data or regulatory coordinator), the staff does not need to be

listed.

5.3.6.3 Hospital staff, including nurses, residents, or fellows and

office staff who provide ancillary or intermittent care but

who do not make a direct and significant contribution to the

data do not need to be listed individually.

5.3.6.4 Any other member of the study team who would makes

clinical decisions during the study. If a question arises as to

if an individual is to be included in this section, please

contact the respective research manager.

5.3.6.4.1 Back-up nurses and/or physicians do not need to be

added if he/she provides intermittent care and does

not make a direct and significant contribution to the

data.

5.3.6.5 Statistician is only listed if he/she is listed on the study as

an investigator.

5.3.6.6 Pharmacist is only listed if he/she is one of the study

investigators or randomizes patients.

5.3.7 Section 7: List the full study title

5.3.7.1 If multiple studies are included under one IND, all studies

associated with that IND should be included.

5.3.8 Section 8: Check one or both boxes which applies (Phase 1, 2 or 3)

dependent upon the clinical phase of the study.

5.3.9 Section10: Obtain principal investigator signature and date.

5.3.10 The original form should be double sided prior to obtaining the

principal investigator’s signature. If the 1572 is comprised of multiple

pages, the pages should be stapled so that there is no question about

what document(s) the investigator signed.

5.4 Subsequent Form Completion

http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM214282.pdf


Page 1 of 3

Title: Regulatory Documentation Management SOP #: RA-9.2.0 Version #: 2.0 Original Approval Date: July 5, 2011 Effective Date: August 5, 2011 Revisions Dates: September 4, 2012


To provide standardized components for all regulatory files/binders for Case Comprehensive Cancer Center investigator-initiated and cooperative group studies, so that they are complete, easy to follow, and contain all necessary documents.

2.0 Scope All cancer-related investigator-initiated and cooperative group research studies.

3.0 Responsibility All department and division personnel responsible for maintaining regulatory documents will utilize this procedure as applicable.


5.0 Procedure

5.1 Regulatory File/Binder Creation 5.1.1 Prior to study initiation, the assigned research personnel will create a regulatory file/binder organized into sections per Section 5.2 5.1.2 If the trial is activated at regional sites, each institution will

adhere to its own regulatory documentation practice. 5.2 Regulatory File/Binder Components

5.2.2 Protocol Section 5.2.2.1 File all IRB approved versions of the protocol in

reverse chronological order. 5.2.3 Delegation of Responsibility and Study Training Log Section

5.2.3.1 File all Delegation of Responsibility and Study Training logs listing all personnel involved in the study with their assigned and authorized responsibilities.

5.2.4 Protocol Review and Monitoring Committee (PRMC) and Institutional Review Board (IRB) Correspondence. 5.2.4.1 File all PRMC and IRB correspondence in reverse

chronological order. 5.2.4.2 This section should begin with the initial new review

PRMC and subsequently IRB submission. 5.2.4.3 IRB approved consent will also be included in this

section. 5.2.4.4 Deviations

5.2.5 Screening and Enrollment Section. 5.2.5.1 Screening (consented subjects) and enrollment log

will be maintained in OnCore.


Page 2 of 3

5.2.5.2 Accrual report should be printed prior to an external monitoring/audit visit.

5.2.6 Drug Accountability Log Section. 5.2.6.1 The original drug accountability log is maintained by

the Research/Investigational Pharmacy. 5.2.7 Financial Disclosures / 1572 Section (IND studies only).

5.2.7.1 1572 and Financial disclosures for all investigators listed on the delegation of responsibility and training log for the trial must be filed in this section.

5.2.8 Sub-Investigator Qualification Documentation (IND studies only) 5.2.8.1 Review and File the current FDA Debarment List

(Drug Product Applications). 5.2.8.2 Complete and File the Investigator Qualification

Checklist. 5.2.9 FDA Correspondence.

5.2.9.1 File all FDA Correspondence in reverse chronological order, the most recent correspondence on top.

5.2.10 Industry supporter / supplier Correspondence. 5.2.10.1 File all drug / device supplier / supporter

correspondence in reverse chronological order. 5.2.11 Monitoring Documentation (as applicable).

5.2.11.1 This should include all monitoring reports and the monitor visit log.

5.2.12 General Correspondence. 5.2.12.1 The general correspondence section should contain

relevant communications not captured in the sections outlined above.

5.2.12.2 Material should be filed by date. 5.2.13 Miscellaneous Section.

5.2.13.1 All other original documents that do not fit into the above listed sections should be maintained under this section.

5.2.13.2 All documents should be filed in reverse chronological order.

5.2.14 Documents that may be located centrally. 5.2.14.1 IRB membership list. 5.2.14.2 Federal Wide Assurance letter. 5.2.14.3 Investigator Brochure. 5.2.14.4 Curriculum Vitae (CV) and Medical License for all

Clinical Laboratory Directors. 5.2.14.5 CLIA/Certification of Anatomic Pathology (CAP)

certificates. 5.2.14.6 Lab normal value(s)/ranges for

medical/laboratory/technical procedure(s) and or test(s) of all participating sites and/or central laboratories.

5.2.14.7 Curriculum Vitae (CV) and Medical License for all Investigators.


SECTION 10: PROTOCOL REVIEW AND MONITORING COMMITTEE (PRMC)



1

Title: Protocol Review and Monitoring Committee Initial Submission

SOP #: PRMC-10.1.0

Version #: 3.0


Effective Date:

August 5, 2011

Revision Dates:

April 7, 2015

April 24, 2017


A procedure documenting the process for submission to the Protocol Review and

Monitoring Committee (PRMC) to assure that the process is consistent and efficient.

2.0 Scope The PRMC reviews all cancer protocols, including protocols sponsored by the national

cooperative oncology groups and the pharmaceutical industry, conducted at the

institutions affiliated with the Case Comprehensive Cancer Center.

Studies that are NCI Peer-reviewed, do not go to full board and are administratively

approved. These include R01s and P01s, CTEP, cooperative group or others deemed by

the Chairs.

Investigator initiated studies from other NCI-designated Cancer Centers that have

undergone the scientific review by their Scientific Review Committee (SRC), do not go

to full board. They are reviewed by the PRMC Chairs who may opt to have the study

reviewed by the full board or other members of the PRMC committee.

Protocols containing research involving only retrospective chart reviews do not require

review by the PRMC and can proceed straight to the IRB. IRB forms and contact info

can be found on the IRB websites at the respective institutions.

3.0 Responsibility Principal Investigator; Regulatory Coordinator; Study Coordinator


5.0 Procedures 5.1 The PRMC submission is sent electronically via email to the PRMC manager and

consists of the submission application including required attachments.

5.1.1 Studies sponsored by other NCI-designated cancer centers must

include their SRC approval letter with submission to the PRMC.

5.1.2 No changes to investigators listed on the PRMC application can be

made until the protocol is reviewed and approved by the PRMC, so as

not to create a conflict of interest when assigning reviewers.

5.1.3 Once a protocol is assigned to an agenda, amendments will not be

accepted for PRMC review until after PRMC review and approval of



2

an initial protocol. See the PRMC Amendment Submission SOP

(PRMC-10.2.0) for specific protocol changes that require PRMC

review.

5.2 Application and other documents can be found on the PRMC webpage at

http://cancer.case.edu/research/clinical-research-office/prmc/

5.3 Submission deadlines and meeting dates are posted on the PRMC webpage.

Meetings are held the 2nd and 4th Tuesdays of the month, except December which

only has one meeting on the 3rd Tuesday.

5.4 Agenda is sent to the Principal Investigator (PI) with meeting logistics at least 10

days before meeting.

5.5 PRMC outcome memos are emailed within 2 days following the initial review.

Trials can either be approved, approved with stipulations, not approved, or

deferred.

5.5.1 If a trial qualifies for administrative review (i.e. CTEP approved,

cooperative group, and others as determined by chair) approval memos

will be generated without the need for full board review.

5.5.2 If a trial is approved with no issues during a full board review,

approval memos will be generated within 2 business days.

5.5.3 If a trial is considered “approved pending resolution of issues”, the

PRMC manager will send the issues to the PI. The PI is responsible for

sending the responses and any revisions to PRMC manager within 90

days of the initial review. The PRMC manager then corresponds with

the original reviewers to determine if the revisions adequately address

the issues. Approval memos are generated once the process is

completed.

5.5.3.1 Responses not returned within 90 days will have to be re-

reviewed at a full board meeting.

5.5.4 If a trial is considered “not approved,” the responses and protocol

revisions will have to undergo an additional full board review by the

PRMC. Same submission requirements and deadlines apply as an

initial review.

5.5.5 If a trial is considered “deferred” (due to lack representation at the

PRMC meeting), it will automatically be postponed to the next

available meeting.

5.6 After the final PRMC approval, the IRB application should be completed and

PRMC approval memo included in the submission. Any responses from the PI

and/or sponsor to issues raised by the PRMC should also be included in the IRB

submission packet.

6.0 References http://cancer.case.edu/research/clinical-research-office/prmc/

http://www.uhhospitals.org/clinical-research/institutional-review-board

http://cancercenters.cancer.gov/documents/PeerReviewFundingOrganizations508C.pdf

https://grants.nih.gov/grants/guide/notice-files/NOT-CA-16-038.html

https://www.cancer.gov/research/nci-role/cancer-centers/find

7.0 Appendices: None


http://www.uhhospitals.org/clinical-research/institutional-review-board

http://cancercenters.cancer.gov/documents/PeerReviewFundingOrganizations508C.pdf

https://grants.nih.gov/grants/guide/notice-files/NOT-CA-16-038.html

https://www.cancer.gov/research/nci-role/cancer-centers/find



1

Title: Protocol Review and Monitoring Committee Amendment Submission

SOP #: PRMC-10.2.0

Version #: 2.0


Effective Date:

August 5, 2011

Revision Dates:

April 7, 2015

June 21, 2017


A procedure documenting the process for an amendment submission to the Protocol

Review and Monitoring Committee (PRMC) to assure that the process is consistent and

efficient.

2.0 Scope Amendments may receive full or administrative review by the PRMC as determined by

the Chair or designate. Amendments from NCI-approved national cooperative groups,

NCI-designated cancer centers or reviewed by CTEP do not require PRMC review and

can proceed straight to the IRB.

The PRMC reviews all amendments that include changes in the following areas:

2.1 Objectives or endpoints

2.2 Biostatistics

2.3 Sample collection

2.4 Treatment/dosing (includes changes to study calendar/time-points)

2.5 Eligibility

3.0 Responsibility: Principal Investigator; Regulatory Coordinator.

4.0 Definitions: None.

5.0 Procedures 5.1 PRMC amendment submission is sent electronically via email to the PRMC

manager. Submission should include a revised tracked and clean protocol with a

summary of changes table included within the protocol or as a separate document.

5.2 PRMC checklist containing outcome of review is emailed to study personnel

within 10 business days. This checklist should be included with the IRB

submission.

6.0 References http://cancer.case.edu/research/clinical-research-office/prmc/

7.0 Appendices: None.




1

Title: Protocol Review and Monitoring Committee Accrual Monitoring

SOP #: PRMC-10.3.0

Version #: 3.0


Effective Date:

November 4, 2011

Revision Dates:

November 12, 2012

April 7, 2015

June 21, 2017


A procedure documenting the process for accrual monitoring by the Protocol Review and

Monitoring Committee (PRMC).

2.0 Scope The PRMC is responsible for monitoring accrual to interventional clinical trials and

mandating closure of studies when low accrual affects the likelihood of successful and

timely completion of the research.

3.0 Responsibility PRMC, Case CCC Clinical Research Leadership Committee, Principal Investigator (PI),

Clinical Trials Units (CTU)

4.0 Definitions 4.1 Case CCC: Case Comprehensive Cancer Center.

4.2 OnCore® Clinical Trials Management System (referred to as OnCore): database to

track information from clinical trials conducted by the Case CCC.

4.3 NCI: National Cancer Institute

4.4 UH: University Hospitals

4.5 CC: Cleveland Clinic

5.0 Procedure 5.1 Reports will be run monthly to review accrual to trials. Accrual to interventional

trials is reviewed every 6 months from study activation. Accrual to sponsored

trials that have not accrued at least 1 patient in the previous 6 months will be

reviewed. Investigator-initiated trials that have not accrued 50% of expected 6-

month accrual will be reviewed.

5.1.1 For sponsored joint trials (between UH and CC) whereas the open to

accrual date is different, each site will be reviewed separately.

Communication between the sites must occur if one side chooses to

close voluntarily. If the PRMC decides the study should be closed at a

particular site, the CTU must communicate with the other site so

regulatory processes can be put in place.

5.1.2 For investigator initiated trials joint (between UH and CC) the PRMC

will monitor from the earliest open date. Decisions will be sent to the
